Impact of Vitamin D on the Occurrence and Development of Intestinal
Diseases: A Systematic Review and Meta-analysis of Randomized
Controlled Trials

Jiewei      Liu; Yue      Wang; Yanhong      Zou; Chunyu      Li

doi:10.2174/1386207326666230123151617

Abstract

Aim: To determine the impact of vitamin D on the occurrence and progression of intestinal disorders, the authors of this study have conducted a systematic review and meta-analysis.

Background: Vitamin D regulates inflammation and immunity in association with reducing the disease symptoms of several gastrointestinal diseases, including inflammatory bowel diseases (IBD), Crohn’s disease (CD), ulcerative colitis (UC), and colorectal cancer (CRC). However, the exact role of vitamin D in the occurrence and development of intestinal diseases is unclear so far.

Methodology: The relevant studies were searched in PubMed and screened based on inclusion and exclusion criteria. The quality of full-text studies was assessed using National Heart, Lung, and Blood Institute (NIH) scale. The study was conducted as per the PRISMA guidelines. The overall estimate was calculated in terms of risk ratio with a 95% confidence interval. The publication bias was assessed qualitatively using a funnel plot, and heterogeneity among studies was calculated using I2 statistics. All analyses were done using RevMan 5.0.

Results: The overall risk ratio using random effect model was found to be 0.89 (0.70, 1.12), which indicates the non-significant role of vitamin D in the occurrence and development of intestinal diseases as compared to the non-vitamin D group. However, after exclusion of studies with low and high sample sizes, a significant reduction in intestinal diseases was observed in the vitamin D group as compared to the non-vitamin D group. Further, no heterogeneity among the studies was observed.

Conclusion: Based on available evidence, vitamin D might play a significant role in the reduction of intestinal diseases; however, more studies with high sample sizes are required to draw a valid conclusion.

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[1]
Chun, R.F.; Liu, P.T.; Modlin, R.L.; Adams, J.S.; Hewison, M. Impact of vitamin D on immune function: Lessons learned from genome-wide analysis. Front. Physiol.,  2014, 5(151), 15.
 [http://dx.doi.org/10.3389/fphys.2014.00151] [PMID:  24795646]

[2]
Ardesia, M.; Ferlazzo, G.; Fries, W. Vitamin D and inflammatory bowel disease. BioMed Res. Int.,  2015, 2015, 1-16.
 [http://dx.doi.org/10.1155/2015/470805] [PMID:  26000293]

[3]
Bernstein, C.N.; Fried, M.; Krabshuis, J.H.; Cohen, H.; Eliakim, R.; Fedail, S.; Gearry, R.; Goh, K.L.; Hamid, S.; Khan, A.G.; LeMair, A.W. Malfertheiner; Ouyang, Q.; Rey, J.F.; Sood, A.; Steinwurz, F.; Thomsen, O.O.; Thomson, A.; Watermeyer, G. World gastroenterology organization practice guidelines for the diagnosis and management of IBD in 2010. Inflamm. Bowel Dis.,  2010, 16(1), 112-124.
 [http://dx.doi.org/10.1002/ibd.21048] [PMID:  19653289]

[4]
Cantorna, M.T.; McDaniel, K.; Bora, S.; Chen, J.; James, J. Vitamin D, immune regulation, the microbiota, and inflammatory bowel disease. Exp. Biol. Med.,  2014, 239(11), 1524-1530.
 [http://dx.doi.org/10.1177/1535370214523890] [PMID:  24668555]

[5]
Dominguez, L.J.; Farruggia, M.; Veronese, N.; Barbagallo, M. Vitamin D sources, metabolism, and deficiency: Available compounds and guidelines for its treatment. Metabolites,  2021, 11(4), 255.
 [http://dx.doi.org/10.3390/metabo11040255] [PMID:  33924215]

[6]
Khalighi Sikaroudi, M.; Mokhtare, M.; Janani, L.; Faghihi, K.A.H.; Masoodi, M.; Agah, S.; Abbaspour, N.; Dehnad, A.; Shidfar, F. Vitamin D3 supplementation in diarrhea-predominant irritable bowel syndrome patients: The effects on symptoms improvement, serum corticotropin-releasing hormone, and interleukin-6 – a randomized clinical trial. Complement. Med. Res.,  2020, 27(5), 302-309.
 [http://dx.doi.org/10.1159/000506149] [PMID:  32203968]

[7]
Sharifi, A.; Vahedi, H.; Nedjat, S.; Mohamadkhani, A.; Hosseinzadeh Attar, M.J.; Vitamin, D. Vitamin D decreases beck depression inventory score in patients with mild to moderate ulcerative colitis: A double-blind randomized placebo-controlled trial. J. Diet. Suppl.,  2019, 16(5), 541-549.
 [http://dx.doi.org/10.1080/19390211.2018.1472168] [PMID:  29958055]

[8]
Sharifi, A.; Vahedi, H.; Nedjat, S.; Rafiei, H.; Hosseinzadeh-Attar, M.J. Effect of single-dose injection of vitamin D on immune cytokines in ulcerative colitis patients: A randomized placebo-controlled trial. Acta Pathol. Microbiol. Scand. Suppl.,  2019, 127(10), 681-687.
 [http://dx.doi.org/10.1111/apm.12982] [PMID:  31274211]

[9]
Ng, K.; Nimeiri, H.S.; McCleary, N.J.; Abrams, T.A.; Yurgelun, M.B.; Cleary, J.M.; Rubinson, D.A.; Schrag, D.; Miksad, R.; Bullock, A.J.; Allen, J.; Zuckerman, D.; Chan, E.; Chan, J.A.; Wolpin, B.M.; Constantine, M.; Weckstein, D.J.; Faggen, M.A.; Thomas, C.A.; Kournioti, C.; Yuan, C.; Ganser, C.; Wilkinson, B.; Mackintosh, C.; Zheng, H.; Hollis, B.W.; Meyerhardt, J.A.; Fuchs, C.S. Effect of high-dose vs standard-dose vitamin D3 supplementation on progression-free survival among patients with advanced or metastatic colorectal cancer. JAMA,  2019, 321(14), 1370-1379.
 [http://dx.doi.org/10.1001/jama.2019.2402] [PMID:  30964527]

[10]
de Bruyn, J.R.; Bossuyt, P.; Ferrante, M.; West, R.L.; Dijkstra, G.; Witteman, B.J.; Wildenberg, M.; Hoentjen, F.; Franchimont, D.; Clasquin, E.; van der Bilt, J.D.; Tollens, T.; Bemelman, W.A.; D’Hoore, A.; Duijvestein, M.; D’Haens, G.R. High-dose vitamin D does not prevent postoperative recurrence of crohn’s disease in a randomized placebo-controlled trial. Clin. Gastroenterol. Hepatol.,  2021, 19(8), 1573-1582.e5.
 [http://dx.doi.org/10.1016/j.cgh.2020.05.037] [PMID:  32461138]

[11]
Karimi, S.; Tabataba-vakili, S.; Ebrahimi-Daryani, N.; Yari, Z.; Karimi, A.; Hedayati, M.; Hekmatdoost, A. Inflammatory biomarkers response to two dosages of vitamin D supplementation in patients with ulcerative colitis: A randomized, double-blind, placebo-controlled pilot study. Clin. Nutr. ESPEN,  2020, 36, 76-81.
 [http://dx.doi.org/10.1016/j.clnesp.2020.02.003] [PMID:  32220372]

[12]
Emami, M.R.; Sharifi, A. yaseri, M.; Derakhshanian, H.; Hosseinzadeh-Attar, M.J. Vitamin D suppresses proangiogenic factors in patients with ulcerative colitis: A randomized double blind placebo controlled clinical trial. Complement. Ther. Clin. Pract.,  2020, 39, 101086.
 [http://dx.doi.org/10.1016/j.ctcp.2020.101086] [PMID:  31957666]

[13]
Pappa, H.M.; Mitchell, P.D.; Jiang, H.; Kassiff, S.; Filip-Dhima, R.; DiFabio, D.; Quinn, N.; Lawton, R.C.; Varvaris, M.; Van Straaten, S.; Gordon, C.M. Treatment of vitamin D insufficiency in children and adolescents with inflammatory bowel disease: A randomized clinical trial comparing three regimens. J. Clin. Endocrinol. Metab.,  2012, 97(6), 2134-2142.
 [http://dx.doi.org/10.1210/jc.2011-3182] [PMID:  22456619]

[14]
Pappa, H.M.; Mitchell, P.D.; Jiang, H.; Kassiff, S.; Filip-Dhima, R.; DiFabio, D.; Quinn, N.; Lawton, R.C.; Bronzwaer, M.E.S.; Koenen, M.; Gordon, C.M. Maintenance of optimal vitamin D status in children and adolescents with inflammatory bowel disease: A randomized clinical trial comparing two regimens. J. Clin. Endocrinol. Metab.,  2014, 99(9), 3408-3417.
 [http://dx.doi.org/10.1210/jc.2013-4218] [PMID:  24926949]

[15]
Tu, H.; Flanders, W.D.; Ahearn, T.U.; Daniel, C.R.; Gonzalez-Feliciano, A.G.; Long, Q.; Rutherford, R.E.; Bostick, R.M. Effects of calcium and vitamin D3 on transforming growth factors in rectal mucosa of sporadic colorectal adenoma patients: A randomized controlled trial. Mol. Carcinog.,  2015, 54(4), 270-280.
 [http://dx.doi.org/10.1002/mc.22096] [PMID:  24166893]

[16]
Ahamed, Z. R.; Dutta, U.; Sharma, V.; Prasad, K.K.; Popli, P.; Kalsi, D.; Vaishnavi, C.; Arora, S.; Kochhar, R. Oral nano vitamin D supplementation reduces disease activity in ulcerative colitis. J. Clin. Gastroenterol.,  2019, 53(10), e409-e415.
 [http://dx.doi.org/10.1097/MCG.0000000000001233] [PMID:  31356558]

[17]
Simek, R.Z.; Prince, J.; Syed, S.; Sauer, C.G.; Martineau, B.; Hofmekler, T.; Freeman, A.J.; Kumar, A.; McElhanon, B.O.; Schoen, B.T.; Tenjarla, G.; McCracken, C.; Ziegler, T.R.; Tangpricha, V.; Kugathasan, S. Pilot study evaluating efficacy of 2 regimens for hypovitaminosis d repletion in pediatric inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr.,  2016, 62(2), 252-258.
 [http://dx.doi.org/10.1097/MPG.0000000000000915] [PMID:  26196201]

[18]
Abbasnezhad, A.; Amani, R.; Hajiani, E.; Alavinejad, P.; Cheraghian, B.; Ghadiri, A. Effect of vitamin D on gastrointestinal symptoms and health-related quality of life in irritable bowel syndrome patients: A randomized double-blind clinical trial. Neurogastroenterol. Motil.,  2016, 28(10), 1533-1544.
 [http://dx.doi.org/10.1111/nmo.12851] [PMID:  27154424]

[19]
Narula, N.; Cooray, M.; Anglin, R.; Muqtadir, Z.; Narula, A.; Marshall, J.K. Impact of high-dose vitamin D3 supplementation in patients with Crohn’s disease in remission: A pilot randomized double-blind controlled study. Dig. Dis. Sci.,  2017, 62(2), 448-455.
 [http://dx.doi.org/10.1007/s10620-016-4396-7] [PMID:  27975236]

[20]
Karimi, S.; Tabataba-Vakili, S.; Yari, Z. The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status. Nutr. J.,  2019, 18(1), 16.
 [http://dx.doi.org/10.1186/s12937-019-0441-7]

[21]
Hosseinzadeh-Attar, M.J.; Sharifi, A.; Vahedi, H.; Nedjat, S. A randomized controlled trial on the effect of vitamin D3 on inflammation and cathelicidin gene expression in ulcerative colitis patients. Saudi J. Gastroenterol.,  2016, 22(4), 316-323.
 [http://dx.doi.org/10.4103/1319-3767.187606] [PMID:  27488327]

[22]
Williams, C.E.; Williams, E.A.; Corfe, B.M. Vitamin D supplementation in people with IBS has no effect on symptom severity and quality of life: Results of a randomised controlled trial. Eur. J. Nutr.,  2022, 61(1), 299-308.
 [http://dx.doi.org/10.1007/s00394-021-02633-w] [PMID:  34328539]

[23]
El Amrousy, D.; Hassan, S.; El Ashry, H.; Yousef, M.; Hodeib, H. Vitamin D supplementation in adolescents with irritable bowel syndrome: Is it useful? A randomized controlled trial. Saudi J. Gastroenterol.,  2018, 24(2), 109-114.
 [http://dx.doi.org/10.4103/sjg.SJG_438_17] [PMID:  29637918]

[24]
Arihiro, S.; Nakashima, A.; Matsuoka, M.; Suto, S.; Uchiyama, K.; Kato, T.; Mitobe, J.; Komoike, N.; Itagaki, M.; Miyakawa, Y.; Koido, S.; Hokari, A.; Saruta, M.; Tajiri, H.; Matsuura, T.; Urashima, M. Randomized trial of vitamin D supplementation to prevent seasonal influenza and upper respiratory infection in patients with inflammatory bowel disease. Inflamm. Bowel Dis.,  2019, 25(6), 1088-1095.
 [http://dx.doi.org/10.1093/ibd/izy346] [PMID:  30601999]

[25]
Sharifi, A.; Vahedi, H.; Honarvar, M.R.; Amiriani, T.; Nikniaz, Z.; Rad, E.Y.; Hosseinzadeh-Attar, M.J. Vitamin D decreases CD40L gene expression in ulcerative colitis patients: A randomized, double-blinded, placebo-controlled trial. Turk. J. Gastroenterol.,  2020, 31(2), 99-104.
 [http://dx.doi.org/10.5152/tjg.2020.181028] [PMID:  32141817]

[26]
Gibbs, D.C.; Fedirko, V.; Baron, J.A.; Barry, E.L.; Flanders, W.D.; McCullough, M.L.; Yacoub, R.; Raavi, T.; Rutherford, R.E.; Seabrook, M.E.; Bostick, R.M. Inflammation modulation by vitamin d and calcium in the morphologically normal colorectal mucosa of patients with colorectal adenoma in a clinical trial. Cancer Prev. Res.,  2021, 14(1), 65-76.
 [http://dx.doi.org/10.1158/1940-6207.CAPR-20-0140] [PMID:  32917645]

[27]
Schöttker, B; Kuznia, S; Laetsch, DC Protocol of the VICTORIA study: Personalized vitamin D supplementation for reducing or preventing fatigue and enhancing quality of life of patients with colorectal tumor - randomized intervention trial. BMC Cancer,  2020, 20(1), 739.
 [http://dx.doi.org/10.1186/s12885-020-07219-z]

[28]
Haidari, F.; Abiri, B.; Iravani, M.; Ahmadi-Angali, K.; Vafa, M. Randomized study of the effect of vitamin D and omega-3 fatty acids cosupplementation as adjuvant chemotherapy on inflammation and nutritional status in colorectal cancer patients. J. Diet. Suppl.,  2020, 17(4), 384-400.
 [http://dx.doi.org/10.1080/19390211.2019.1600096] [PMID:  31106659]

[29]
Wingate, K.E.; Jacobson, K.; Issenman, R.; Carroll, M.; Barker, C.; Israel, D.; Brill, H.; Weiler, H.; Barr, S.I.; Li, W.; Lyon, M.R.; Green, T.J. 25-Hydroxyvitamin D concentrations in children with Crohn’s disease supplemented with either 2000 or 400 IU daily for 6 months: A randomized controlled study. J. Pediatr.,  2014, 164(4), 860-865.
 [http://dx.doi.org/10.1016/j.jpeds.2013.11.071] [PMID:  24423431]

[30]
Mandle, H.B.; Jahan, F.A.; Bostick, R.M.; Baron, J.A.; Barry, E.L.; Yacoub, R.; Merrill, J.; Rutherford, R.E.; Seabrook, M.E.; Fedirko, V. Effects of supplemental calcium and vitamin D on tight‐junction proteins and mucin‐12 expression in the normal rectal mucosa of colorectal adenoma patients. Mol. Carcinog.,  2019, 58(7), mc.23010.
 [http://dx.doi.org/10.1002/mc.23010] [PMID: 30938860]

[31]
Song, M.; Lee, I.M.; Manson, J.E.; Buring, J.E.; Dushkes, R.; Gordon, D.; Walter, J.; Wu, K.; Chan, A.T.; Ogino, S.; Fuchs, C.S.; Meyerhardt, J.A.; Giovannucci, E.L. No association between vitamin D supplementation and risk of colorectal adenomas or serrated polyps in a randomized trial. Clin. Gastroenterol. Hepatol.,  2021, 19(1), 128-135.e6.
 [http://dx.doi.org/10.1016/j.cgh.2020.02.013] [PMID:  32062040]

[32]
Gao, Y; Um, CY; Fedirko, V Effects of supplemental vitamin D and calcium on markers of proliferation, differentiation, and apoptosis in the normal colorectal mucosa of colorectal adenoma patients. PLoS One,  2018, 13(12), e0208762.
 [http://dx.doi.org/10.1371/journal.pone.0208762]

[33]
Urashima, M.; Ohdaira, H.; Akutsu, T.; Okada, S.; Yoshida, M.; Kitajima, M.; Suzuki, Y. Effect of vitamin D supplementation on relapse-free survival among patients with digestive tract cancers. JAMA,  2019, 321(14), 1361-1369.
 [http://dx.doi.org/10.1001/jama.2019.2210] [PMID:  30964526]

[34]
Ahearn, T.U.; Shaukat, A.; Flanders, W.D.; Rutherford, R.E.; Bostick, R.M. A randomized clinical trial of the effects of supplemental calcium and vitamin D3 on the APC/β-catenin pathway in the normal mucosa of colorectal adenoma patients. Cancer Prev. Res.,  2012, 5(10), 1247-1256.
 [http://dx.doi.org/10.1158/1940-6207.CAPR-12-0292] [PMID:  22964475]

[35]
Baron, J.A.; Barry, E.L.; Mott, L.A.; Rees, J.R.; Sandler, R.S.; Snover, D.C.; Bostick, R.M.; Ivanova, A.; Cole, B.F.; Ahnen, D.J.; Beck, G.J.; Bresalier, R.S.; Burke, C.A.; Church, T.R.; Cruz-Correa, M.; Figueiredo, J.C.; Goodman, M.; Kim, A.S.; Robertson, D.J.; Rothstein, R.; Shaukat, A.; Seabrook, M.E.; Summers, R.W. A trial of calcium and vitamin D for the prevention of colorectal adenomas. N. Engl. J. Med.,  2015, 373(16), 1519-1530.
 [http://dx.doi.org/10.1056/NEJMoa1500409] [PMID:  26465985]

[36]
Jørgensen, S.P.; Agnholt, J.; Glerup, H.; Lyhne, S.; Villadsen, G.E.; Hvas, C.L.; Bartels, L.E.; Kelsen, J.; Christensen, L.A.; Dahlerup, J.F. Clinical trial: Vitamin D3 treatment in Crohn’s disease - a randomized double-blind placebo-controlled study. Aliment. Pharmacol. Ther.,  2010, 32(3), 377-383.
 [http://dx.doi.org/10.1111/j.1365-2036.2010.04355.x] [PMID:  20491740]

[37]
Bendix-Struve, M.; Bartels, L.E.; Agnholt, J.; Dige, A.; Jørgensen, S.P.; Dahlerup, J.F. Vitamin D3 treatment of Crohn’s disease patients increases stimulated T cell IL-6 production and proliferation. Aliment. Pharmacol. Ther.,  2010, 32(11-12), 1364-1372.
 [http://dx.doi.org/10.1111/j.1365-2036.2010.04463.x] [PMID:  21050239]

[38]
Dadaei, T.; Safapoor, M.H.; Asadzadeh Aghdaei, H.; Balaii, H.; Pourhoseingholi, M.A.; Naderi, N.; Zojaji, H.; Azimzadeh, P.; Mohammadi, P.; Zali, M.R. Effect of vitamin D3 supplementation on TNF-α serum level and disease activity index in Iranian IBD patients. Gastroenterol. Hepatol. Bed Bench,  2015, 8(1), 49-55.
 [PMID:  25584176]

[39]
Jalili, M.; Vahedi, H.; Poustchi, H.; Hekmatdoost, A. Effects of vitamin D supplementation in patients with irritable bowel syndrome: A randomized, double-blind, placebo-controlled clinical trial. Int. J. Prev. Med.,  2019, 10, 16.
 [http://dx.doi.org/10.4103/ijpvm.IJPVM_512_17]

[40]
Lu, C.; Yang, J.; Yu, W. Association between 25(oh)d level, ultraviolet exposure, geographical location, and inflammatory bowel disease activity: A systematic review and meta-analysis. PLoS One,  2015, 10(7), e0132036.
 [http://dx.doi.org/10.1371/journal.pone.0132036]

[41]
Heine-Bröring, R.C.; Winkels, R.M.; Renkema, J.M.S.; Kragt, L.; van Orten-Luiten, A.C.B.; Tigchelaar, E.F.; Chan, D.S.M.; Norat, T.; Kampman, E. Dietary supplement use and colorectal cancer risk: A systematic review and meta-analyses of prospective cohort studies. Int. J. Cancer,  2015, 136(10), 2388-2401.
 [http://dx.doi.org/10.1002/ijc.29277] [PMID:  25335850]

[42]
Del, P.R.; Pietropaoli, D.; Chandar, A.K.; Ferri, C.; Cominelli, F. Association between inflammatory bowel disease and vitamin D deficiency. Inflamm. Bowel Dis.,  2015, 21(11), 2708-2717.
 [http://dx.doi.org/10.1097/MIB.0000000000000546] [PMID:  26348447]

[43]
Cho, Y.A.; Lee, J.; Oh, J.H. Vitamin D receptor FokI polymorphism and the risks of colorectal cancer, inflammatory bowel disease, and colorectal adenoma. Sci. Rep.,  2018, 8(1), 12899.
 [http://dx.doi.org/10.1038/s41598-018-31244-5]

[44]
Lu, C.; Zhou, W.; He, X.; Zhou, X.; Yu, C. Vitamin D status and vitamin D receptor genotypes in celiac disease: A meta-analysis. Crit. Rev. Food Sci. Nutr.,  2021, 61(12), 2098-2106.
 [http://dx.doi.org/10.1080/10408398.2020.1772716] [PMID:  32508121]

[45]
Guo, Y.; Zhang, T.; Wang, Y.; Liu, R.; Chang, M.; Wang, X. Effects of oral vitamin D supplementation on inflammatory bowel disease: A systematic review and meta-analysis. Food Funct.,  2021, 12(17), 7588-7606.
 [http://dx.doi.org/10.1039/D1FO00613D] [PMID:  34231596]

[46]
Lopez-Caleya, J.F.; Ortega-Valín, L.; Fernández-Villa, T.; Delgado-Rodríguez, M.; Martín-Sánchez, V.; Molina, A.J. The role of calcium and vitamin D dietary intake on risk of colorectal cancer: Systematic review and meta-analysis of case–control studies. Cancer Causes Control,  2022, 33(2), 167-182.
 [http://dx.doi.org/10.1007/s10552-021-01512-3] [PMID:  34708323]

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DOI https://dx.doi.org/10.2174/1386207326666230123151617	Print ISSN 1386-2073
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Impact of Vitamin D on the Occurrence and Development of Intestinal Diseases: A Systematic Review and Meta-analysis of Randomized Controlled Trials

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